Gating of Membrane Protein Polyhedral Nanoparticles

Membrane proteins and lipids can self-assemble into membrane protein polyhedral nanoparticles (MPPNs)—closed lipid bilayer vesicles with a polyhedral arrangement of membrane proteins. The closed surfaces of MPPNs, together with their well-defined symmetry and characteristic size, may permit structural studies of membrane proteins in the presence of transmembrane gradients. In particular, transmembrane gradients can be used to stabilize distinct conformational states of membrane proteins in MPPNs, such as the closed and open states of ion channels. We describe here a computational model of MPPN symmetry inspired by previous work on viral capsid self-assembly. Our model allows us to systematically explore the preferred symmetry of MPPNs as a function of the number of open and closed ion channels in MPPNs, and the difference in size of open and closed ion channels. Our results suggest practical strategies for the utilization of MPPNs as a novel method for the structural analysis of membrane proteins in controlled conformational states.